NCCAM has identified as a high priority research area the evaluation of various formulations of turmeric/curcumin for the treatment of musculoskeletal pain, including comparisons of bioavailability and pharmacokinetic parameters, with the goal of identifying an appropriate patient population, optimizing the intervention, and identifying appropriate outcome measures for a larger clinical trial. Using an experimental model of rheumatoid arthritis (RA), the PI of this current proposal has previously performed a detailed analysis of the anti-inflammatory effects of turmeric/curcumin in RA, a particularly inflammatory and joint destructive form of arthritis, in NCCAM/ODS-funded studies examining efficacy, bioactive moieties and mechanism of action. We now propose to build upon this knowledge base, translating our findings into the clinical arena in a preliminary study assessing the feasibility and tolerability of turmeric/curcumin use in RA, including an initial assessment of doses, bioavailability of curcuminoids and potentially bioactive metabolites, and estimates of effect size on known RA biomarkers of anti-inflammatory activity. A two-arm doubled blinded pilot study assessing two doses of a commercially available curcuminoid formulation with enhanced bioavailability is proposed. Project year 1 will be an administrative period devoted to obtaining IND and IRB approval, as well a finalization of all protocol related documents. Project Years 2-3 will be devoted to the clinical trial itself, which will examine the feasibility and tolerability of administering curcuminoids to biologic naive RA patients with active disease who have inadequately responded to methotrexate, including pharmacokinetic studies and estimates of effect size on known inflammatory biomarkers. The ultimate goal of this clinical planning study is to obtain data to guide the design of a large clinical trial (Curcuma longa L. in Rheumatoid Arthritis [CLaRA]) assessing the anti-arthritic effects of curcuminoids in the treatment of joint pain and inflammation in a chronic inflammatory musculoskeletal disorder, rheumatoid arthritis.